CEREBRAL BLOOD FLOW AND METABOLISM...Cerebral Angiography Cerebral angiography is a procedure that...
Transcript of CEREBRAL BLOOD FLOW AND METABOLISM...Cerebral Angiography Cerebral angiography is a procedure that...
CEREBRAL BLOOD FLOW
AND METABOLISM
Part 3 - 2016
Structural
Magnetic resonance imaging (MRI)
Computed tomography (CT)
Ultrasound
Functional
Functional MRI
Positron emission tomography (PET)
Single photon emission computed
tomography (SPECT)
Electroencephalography (EEG)
Magnetoencephalography (MEG)
Neuroimaging Techiques
Cerebral Angiography
Cerebral angiographyis a procedure thatuses a special dye(contrast material) and x-rays to see howblood flows through thebrain.
Cerebral angiogram: obtained using an iodine based contrastmedium.
The cerebral angiogram
of an 87-year-old man
with acute onset left
hemiplegia.
A: preoperatively,
middle cerebral artery
occlusion (no collateral
supply)
B: after intra-arterial
thrombolysis. One
segment has
recanalized with
restoration of blood flow
to the superior division,
but a persistent
occlusion in the inferior
division
Cerebral Angiography – Case Report
short arrow: right internal carotid artery
long arrow: middle cerebral artery
arrowhead: anterior cerebral artery
Cerebral Angiography – Case Report
short arrow: left vertebral artery
long arrow: basilar artery
arrowhead: posterior inferior cerebellar
arteries
white arrow: posterior cerebral arteries
white arrowhead: superior cerebellar
arteries
The cerebral
angiogram of a 67-
year-old woman
presenting with
acute onset
unresponsiveness
and quadriparesis.
A: occlusion at the
mid-basilar level
with absent flow to
the distal basilar
artery as well as the
distal branches of
the basilar arteryB: post-thrombolysis, complete
recanalization of the basilar artery
Computed Tomography
http://fitsweb.uchc.edu/student/selectives/TimHerbst/intro.htm
Tomography
~ Imaging in sections,
or slices
Computed
~ Computerized
algorithms: geometric
processing used to
reconstruct an image
Computed Tomography
Uses X-rays
Dense tissue, like bone, blocks x-rays.
Gray matter weakens (attenuates) the x-rays.
Fluid attenuates even less
A computerized algorithm (filtered back
projection) reconstructs an image of each
slice.
CT Image Formation
X-ray detectorX-ray
X-ray tube
CT Image Formation
Reconstruction
matrix
CT Image Reconstruction – 6 Slices
CT Image Reconstruction – 12 Slices
CT Image Reconstruction – Final Image
Perfusion CT
Perfusion computed tomography (CT) allows rapid qualitative and
quantitative evaluation of cerebral perfusion by generating maps of cerebral
blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT).
The examination is based on the indicator dilution theory: iv. administration of
contrast medium → the X-ray density of the brain temporarily increases.
Mathematical
algorithms:
parameters denoting
cerebral perfusion
are calculated and
represented in the
form of color-coded
parameter images.
Stroke: border of damage
CT Angiography
Computed tomography
angiography (CTA) is a
computed tomography
technique used to
visualize arterial and
venous vessels
throughout the body.
Precise anatomical images
available (to determine vessel
diameter, the surrounding soft
tissue structures and bony
parts)
CT Angiography
Benefits
Examination of blood
vessels in many key areas
(eg. brain, kidneys, lungs)
Displays the anatomical
detail of blood vessels
more precisely than other
techniques (MRI or
ultrasound)
Risks
Risk of an allergic reaction
(contrast material
containing iodine)
Contrast material can
harm kidney (kidney
disease or diabetes)
Associated with a
significant dose of ionizing
radiation
CT – Case Report
Perfusion-CT demonstrates
mixed infarct and penumbra in
the left side, whereas CT-
angiography relates it to an
occlusion (arrow).
After intravenous thrombolysis:
recanalization of the left sylvian
artery. Follow-up perfusion CT
shows an almost complete
resolution of the penumbra.
Max Wintermark: Brain Perfusion Computed Tomography for the Management of Acute Stroke Patients. US
Neurology Review 2005
Modern imaging methods
SPECT, PET, nMRI
History of Nuclear Medicine
Starts with the invention of the X-ray
1946: radioactive iodine was used to treat a patient’s thyroid cancer
1950’s: radioactive nucleotides were being used to treat hyperthyroidism
Soon after: snapshot images of form and structure or organs (liver, spleen, brain, gastrointestinal track, ect.)
1980’s: nuclear medicine cameras and imaging computers
allowed for the instillation of over 100 different procedures
Nuclear medicine became an integral part of patient care, and
an important diagnostic and therapeutic specialty.
Single Photon-Emitted Computed
Tomography (SPECT)
Tomographic imaging technique
using gamma rays. It is very
similar to conventional nuclear
imaging using a gamma camera
(however, it is able to provide
true 3D information).
The technique requires injection
of a gamma-emitting
radioisotope into the
bloodstream of the patient, to be
carried and bound to a place of
interest in the body, which then
allows the ligand concentration
to be seen by a gamma-camera.
Gamma Camera
Gamma camera (~scintigraphy) is a device
used to image gamma radiation emitting
radioisotopes.
Information on the position and
intensity of incident gamma-ray is
recorded by Flat Panel Display
Back projection is performed from
forward projection data into the
space confined by collimators
Collimator: Lead (tungsten or platinum)
Narrows a beam of particles or waves
Excludes erroneous gamma rays
Determines spatial resolution to detection
efficiency ratio
NaI(Tl) crystals
convert the energy deposited by a high energy
gamma ray into a large number of lower energy
photons
Photomultiplier tubes
multiply the current produced by incident light by
as much as 100 million times
Transform photons to electrical signals using
photocathode
Gamma Camera - Components
Display
Computer
Head
Collimator
NaI Crystal
Photomultiplier
tubes
Image Reconstruction
Gamma rays are counted into matrix
Filtering
Convolution Method (9 point smoothing)
Fourier Method
Digital vs. Annalog
Too few pixels
Too few bytes per pixel
Radioisotopes
Simple soluble dissolved ion
Also have chemical properties that
allow it to be concentrated in ways
of medical interest for disease
detection
However, most of the time in
SPECT, a marker radioisotope
(radioactive properties) has been
attached to a special radioligand
(chemical binding properties to
certain types of tissues)
Targeted for different tissues
Isotope Activity Half-lifeEnergies
(KeV)
Barium-133 1uCi 10.7 years 81.0, 356.0
Cadmium-109 1uCi 453 days 88.0
Cobalt 57 1uCi 270 days 122.1
Cobalt 60 1uCi 5.27 years1173.2,
1332.5
Europium-152 1uCi 13.5 years
121.8,
344.3,
1408.0
Manganese-54 1uCi 312 days 834.8
Sodium-22 1uCi 2.6 years511.0,
1274.5
Zinc-65 1uCi 244 days511.0,
1115.5
Technetium 99m 1uCi 6.01 hours 140
History of SPECT
Edwards and Kuhl developed the MARK VI, the first
Emission Computed Tomography (ECT) device
consisted of several sodium iodide photon detectors
arranged in the rectangular shape around the head of
the patient
Tomomatic-32, first SPECT imaging device, was similar to
the MARK VI but had 32 photon detectors
ECT was discredited due to unusable images
Gained acceptance once X-ray CT image reconstruction
algorithms were applied to ECT to take into account for
attenuation for scatter in the body
Technological Advances
Problems:
Long scan times
Low resolution
Attenuation
Solutions:
Triple headed cameras
drastically reduce scan times
Improved cameras and
computers enhance resolution
Visual Tracking Systems to
monitor patient movement and
correct images accordingly
Attenuation Correction software
SPECT
Benefits
ECT produces 3-D images that relate an organ’s function
Allows for better relay of extent of disease and reveals the course of the disease earlier
Large amount of data on brain function
Simple process with immediate results
Much less expensive than MRI or PET
Risks
Unlike MRI and X-ray, there is an injection
Claustrophobia is a cause for concern
Quality of image can be lessened by patient movement
Clinical Applications
In the 70’s & 80’s, SPECT was largely replaced
by CAT and MRI scans because they provided
superior resolution
Recently, SPECT has returned to prominent
use, especially in diagnosing cardiac and
neurological abnormalities
While CAT and MRI scans only provide images
of static brain anatomy, SPECT offers clues to
brain function by tracing blood allocation
Types of brain SPECT images:
Surface Image: Active Image:
Full symmetrical activity across
cortical surface
High activity in cerebellum and
visual or occipital cortex
Examiners look for too much/little activity in a certain area,
or asymmetry in areas that should be symmetrical.
SPECT Images of Common Neurological
and Psychiatric Disorders
Right Sided Stroke Alzheimer’s Disease
pervasive hypoperfusion
Head Trauma
to left PFC - severe
aggression problems/violence
Depression
increased limbic activity (left) and decreased
prefrontal and temporal lobe activity
SPECT Images of Common Neurological
and Psychiatric Disorders
Schizophrenia
Before (left) and after (right)
medication
Attention deficit hyperactivity disorder
Normally (left) and while performing
a concentration task (right)
Alcohol Marijuana Cocaine Heroin
SPECT Images of Common Neurological
and Psychiatric Disorders
Positron Emission Tomography
PET - nuclear medicine imaging technique that
produces a 3D image or picture of functional
processes in the body
Detects pairs of
gamma rays emitted
indirectly by a
positron-emitting
radionuclide (which is
introduced into the body on a
biologically active molecule)
PET Scan of the Brain
Using radionuclide (FDG – Fluodeoxyglucose –18F) that is like glucose, the PET scan will show how the tissues in the brain are functioning
Areas of less function use less energy, and areas with increased metabolic activity use more energy
Radiopharmaceuticals
Radionuclide
11C half-life ~20 min
13N 10 min
15O 2 min
18F 110 min
Localization
Biochemical metabolism within
the cell
Adult Dose Range
5-15 mCi (185-555 MBq)
+ glucose, water,
ammonia or other
molecule =
radiotracersThe half-life of 18F is long enough that radiotracers can be
manufactured commercially at offsite locations and shipped to
imaging centers.
Evaluation of cerebrovascular diseaseStrokesTransient ischemic attacks (TIAs)
Evaluation of epilepsy
Evaluation of movement disorders Huntington Parkinson
Evaluation of psychiatric disorders Schizophrenia Mood disorders
Indications in the CNS
Stroke
Epilepsy
Indications in the CNS
Evaluation of dementia Alzheimer’s disease
Evaluation of tumors Evaluation of grade and extend of glioma
Evaluation of chemotherapy
To locate the specific surgical site prior to surgical procedures of the brain
To evaluate the brain after trauma to detect hematoma (blood clot), bleeding, and/or perfusion (blood and oxygen
Alzheimer’s disease
Tumor
flow) of the brain tissue
Before the PET Examination
The patient must fast six hours prior to the appointment
time except water!
In addition, patient should avoid any carbohydrates from
his/her diet (e.g., bread, pasta, potatoes and rice) 24
hours prior to the appointment time, because
carbohydrates taken before the test will reduce the
effectiveness of it!
Brain 3D
One of the most exciting methodological advances for brain research has been in functional brain imaging; itenables the localization and characterization of neural activity in the living human brain
Recently developed 3D-PET imaging techniques using H2
15O and 18F-FDG make it possible to visualize the brain activity associated with cognitive processes
We will visualize functional neuroanatomy of subjective feelings of sleepiness, visceral perception, itching, and emotion using H2
15O
Functional neuroanatomy of subjective
feelings using 3D-PET
3D PET in Diagnostics of Epilepsy
During a seizure, the area responsible for the seizure will show up as an area of increased glucose use
Between the seizures, PET shows a characteristic pattern of reduced need for glucose
Epilepsy
Alzheimer’s Disease
Diminished FDG uptake in thetemporal lobeswhich arecompatible withAlzheimer’sdisease
PET scan of a healthy brain compared to a brain at an early stage of Alzheimer's disease
Parkinson’s disease
Normal Parkinson’s disease
18F-AV-133 images of vesicular monoamine transporters acquired 90–
120 minutes post injection in a normal elderly subject (left) and a patient
with mild Parkinson’s disease (right) demonstrating a dramatic reduction
in dopaminergic innervation to the striatum
Brain Tumor
Contraindications
Patient too agitated, uncooperative, or
claustrophobic to remain still for acquisition
Because PET involves cellular metabolism,
drugs and food ingestion, or lack thereof,
bears specific consideration for each study
SPECT vs. PET
PET uses beta-plus-emitting radionuclides
such as 11C, 13N, 15O, and 18F which annihilate
into two 511-keV photons that travel in
opposite directions
SPECT involves detection of gamma rays
emitted singly from radionuclides such as 99mTc, 123I, and 111In
NMR = nuclear magnetic resonance
nuclear: properties of nuclei of atoms
magnetic: magnetic field required
resonance: interaction between
magnetic field and radio frequency
Bloch Purcell
NMR MRI
Source: Jody Culham’s web slides
History of Nuclear Magnetic Resonance
Felix Block and Edward Purcell
• 1946: atomic nuclei
absorb and re-emit radio
frequency energy
• 1952: Nobel prize in
physics
MRI
• 1973: Lauterbur suggests NMR could be used to form images
• 1977: clinical MRI scanner patented
• 1977: Mansfield proposes echo-planar imaging (EPI) to acquire images
faster
fMRI
• 1990: Ogawa observes BOLD effect with T2*
blood vessels became more visible as blood oxygen decreased
• 1991: Belliveau observes first functional images using a contrast agent
• 1992: Ogawa & Kwong publish first functional images using BOLD signal
History of fMRI
Source: Jody Culham’s web slides
Longitudinal magnetization~B0 - is used to denote the main
magnetic field
objects placed within B0 will gradually align to this field
(longitudinal relaxation)
M0 – is used to denote the net magnetization of an object within B0
M0 is ‘tipped’ out of alignment with B0 to create the MR
image – so M0 is now measured as transverse magnetization
RF pulse – radio frequency pulse (not to be confused with ‘resonant frequency’)
to read M0 it must be tipped out of alignment with B0 – this is
achieved by sending an RF pulse at certain resonant
frequencies and gradients
Some Terms to Know
Some Terms to Know
Magnet – the big magnet that we allocate the Tesla value to that
creates B0
Gradient Coil – smaller magnets that are used to tip the net
magnetization of the subject (M0) out of alignment with B0
There are actually three gradient coils orthogonal to one
another so that gradients can be applied in the x, y and z
planes
RF coil – radio frequency coil – these are typically receive only
coils and are used to measure M0 at some time after the RF
pulses have been applied. Send/receive coils are also available
Physics of Protons
• motion of electrically charged particles results in a
magnetic force orthogonal to the direction of motion
• protons (nuclear constituent of atom) have a property
of angular momentum known as spin
Angular momentum (spin) of a proton.
Protons Aligning within a Magnetic
Field
In “field free” space
randomly oriented
Source: Mark Cohen’s, Robert Cox’s, Jody Culham’s web slides
• when placed in a magnetic field (B0; e.g., our MRI machines) protons will either
align with the magnetic field or orthogonal to it (process of reaching magnetic
equilibrium)
• there is a small difference (10:1 million) in the number of protons in the low and
high energy states – with more in the low state leading to a net magnetization (M)
oriented with or against B0
M = net magnetization
M
Applied Magnetic
Field (B0)
Inside magnetic field
Precession – the Spinning Top
Analogy
Source: Cohen and Bookheimer article
What is actually aligned with the B0 is the axis around which the proton
precesses – the decay of precession (i.e., it is the rate of precession out of
alignment with B0 together with the proton density of the tissue concerned
that is crucial in MRI)
Larmor equation
f = B0
= 42.58 MHz/T
At 1.5T, f = 63.76 MHz
At 4T, f = 170.3 MHz
Field Strength (Tesla)
Resonance
Frequency for 1H
170.3
63.8
1.5 4.0
• the energy difference between the high (oriented with B0) and low
(oriented against B0) energy protons is measurable and is expressed in
the Larmor equation
Larmor Frequency
protons can flip between low and high energy states
(i.e., flip between being aligned with or against B0)
to do so the energy transfer must be of a precise
amount and must be facilitated by another force
(e.g., other protons or molecules)
in MRI, RF (radio frequency) pulses are used to
excite the RF field – the Swing analogy – tipping the
net magnetization out of alignment with B0
RF Excitation
Cox’s Swing Analogy
Person sitting on swing at rest is
„aligned” with externally imposed
force field (gravity)
To get the person up high, you could
simply supply enough force to
overcome gravity and lift him (and the swing) upAnalogous to forcing M over by turning on a huge static B1
The other way is to push back and forth with a tiny
force, synchronously with the natural oscillations of
the swingAnalogous to using tiny B1 to slow flip M over
Excite Radio Frequency (RF) field• transmission coil: apply magnetic field along B1 (perpendicular to B0) for ~3
ms
• oscillating field at Larmor frequency
• frequencies in range of radio transmissions
• B1 is small: ~1/10,000 T
• tips M to transverse plane – spirals down
• analogies: guitar string (Noll), swing (Cox)
• final angle between B0 and B1 is the flip angle
B1
B0
Source: Robert Cox’s web slides
RF Excitation
Longitudinal relaxation and T1
• temperature influences the number of collisions (and hence the rate
at which protons flip between low and high energy states)
• so magnetic equilibrium (M0), or the rate at which a body placed
inside B0 becomes magnetized depends on temperature – this is
known as longitudinal relaxation
• the T1-weighted image (usually used for anatomical images)
measures the rate at which the object placed in B0 (the unsuspecting
subject in our case) goes from a non-magnetized to a magnetized
state – the longitudinal relaxation
• different types of molecules (and by extension tissue) approach M0 at
different rates allowing us to differentiate things like white and grey
matter – we creep close towards the image!!!
T1 and T2
T1 measures the longitudinal relaxation (along B0) – or the rate at which the
subject (and the various different constituents of that subject) reaches
magnetic equilibrium
T2 measures the transverse relaxation (along B1) – or the rate of decay of the
signal after an RF pulse is delivered
T1 – recovery to state of magnetic equilibrium
T2 – rate of decay after excitation
Tissue T2 decay times (in 1.5 T magnet)
white matter 70 msec
grey matter 90 msec
CSF 400 msec
Reading M0
RF coils receive the net magnetization from the object placed within the
coil (e.g., a subject’s head)
can also have send / receive RF coils that also deliver the RF pulse (to
get the swing going) – usually the pulse is delivered by gradient coils
Proton density, recovery (T1) and decay
(T2 and T2*) times.
By ‘weighting’ the pulse sequence (and point at which data is collected)
different images of the brain are obtained
Weighting is achieved by manipulating TE (time to echo) and TR (time to
repetition of the pulse sequence)
T1 weighted Density weighted T2 weighted
Precession In and Out of Phase
Source: Mark Cohen’s web slides
all nuclei aligned and precessing
in the same direction.
nuclei not aligned but still precessing
in the same direction.
So MR signal will start off strong but as protons begin to precess out of
phase the signal will decay.
T1 and TR
Source: Mark Cohen’s web slides
T1 = recovery of
longitudinal (B0)
magnetization after the
RF pulse
• used in
anatomical images
• ~500-1000
msec (longer with
bigger B0)
TR (repetition time) =
time to wait after
excitation before
sampling T1
T2 and TE
Source: Mark Cohen’s web slides
T2 = decay of transverse
magnetization after RF
pulse
TE (time to echo) = time
to wait to measure T2 or
T2* (after re-focusing
with spin echo)
T1 vs. T2
Effectively, T1 and T2 images are the inverse of one another, with T1
typically used to form anatomical images and T2* used in fMRI
T1 and TR
T2: intrinsic decay of transverse magnetization over microscopic region
(~5-10 microns)
~50-100 msec (shorter with bigger B0)
T2*: overall decay of transverse magnetization over macroscopic region
(~mm)
decays more quickly than T2 (by factor of ~2)
Source: Robert Cox’s web slides
T2*
MRI - Image Formation
When the RF pulse is turned off, the hydrogen
protons return to their natural alignment within
the magnetic field.
Energy is released.
The coil detects this signal and sends it to a
computer for processing.
The signal consists of complex values which
have real and imaginary components.
MRI Image Formation
Magnitude information from signal
Phase information from signal
Fourier
Transform
MRI Visualization
A series of 2D MRI
images can be
combined together to
form a 3D volume
This volume can then
be used to generate
realistic visualizations
and models
MRI - Benefits
Excellent for clearly visualizing structures in
soft tissues, such as the brain
Very commonly used in:Diagnosis
Image-guided surgery and therapy
By adjusting scanning settings, specific
features can be detected
MRI images are 2D slices through the body at
a specific location
MRI Scanner
http://psyphz.psych.wisc.edu/
MRI - Cases
CT scan of a patient who has had a
left middle cerebral artery stroke.
The arrow indicates the location of
the stroke.
MRI of a patient who has had a
stroke of the left hemisphere of the
brain. The arrow indicates the area
that was affected.
BOLD Functional MRI
BOLD Functional MRI
Magnetic properties of oxyhemoglobin and
deoxyhemoglobin:
L. Pauling and C. Coryell, PNAS USA 22:210-216 (1936)
BOLD effects in vivo:
S. Ogawa, et al., MRM, 14:68-78 (1990)
BOLD activation experiments:
K. K. Kwong, et al., PNAS USA, 89:5675-5679 (1992)
S. Ogawa, et al., PNAS USA, 89:5951-5955 (1992)
P. A. Bandettini, et al., MRM, 25:390-397 (1992)
J. Frahm, et al., JMRI, 2:501-505 (1992)
Mechanism of BOLD Functional MRI
Brain activity
Oxygen consumption Cerebral blood flow
Oxyhemoglobin
Deoxyhemoglobin
Magnetic susceptibility
T2*
MRI signal intesity
Magnetic Properties of Oxyhemoglobin
and Deoxyhemoglobin
Deoxyhemoglobin: paramagnetic (c > 0)
paramagnetic with respect to the surrounding
tissue
Oxyhemoglobin: diamagnetic (c < 0)
isomagnetic with respect to the surrounding
tissue
Magnetic Susceptibility
cdiamagneti 0,χ icparamagnet 0,χ if
χHM
Oxyhemoglobin and Deoxyhemoglobin in
Veins during Brain Activation
Oxyhemoglobin
Deoxyhemoglobin
Rest Activation
Normal blood flow High blood flow
T2* Effect in fMRI
excitation reception
MR
sig
nal (S
)
action
rest
TE t
Time Series and Activation Maps
Off Off Off OffOn On On On
Scan Number
Sig
nal In
ten
sit
y
Challenges in Functional FMRI
Sensitivity (Contrast-to-noise ratio)BOLD signal change is ~1-2% at 1.5 T; signal-to-noise ratio in single-shot
echo-planar images images (EPI) is ~100.
Physiological pulsations (cardiac and respiratory); Head motion; instrumental
instability
Specificity
Location of activation – neurons or veins
Susceptibility artifacts
Challenges in Functional FMRI
Temporal resolution
Limited by BOLD impulse-response
function, image sampling rate, and spin relaxation
times
Spatial resolution
Limited by BOLD point-spread function,
signal-to-noise ratio, and image sampling rate
Non-linearity
Neurological and hemodynamic
Acoustic noise